PDF(Pubmed)
Abstract：
ERBB2 amplification is one of the most important and mature targets for HER2-targeted drug therapy. Somatic mutations of ERBB2 in the tyrosine kinase domain have been studied extensively, and play a role in response to anti-HER2 therapy among different cancer types. However, ERBB2 fusion has not been got attention and its relevance to HER2-targeted therapy is unclear. We comprehensively characterized ERBB2 fusions from next-generation sequencing (NGS) data between May 2018 and October 2021 in 32,131 various solid tumors. Among the tumors, 0.28% harbored ERBB2 fusions, which occurred more commonly in gastroesophageal junction cancer (3.12%; 3/96), breast cancer (1.89%; 8/422), urothelial carcinoma (1.72%; 1/58), and gastric cancer (1.60%; 23/1,437). Our population presented with a median age of 65 years (range 28 to 88 years), a high proportion of men (55 men vs 34 women; 61.80%). Among the patients with ERBB2 fusions, TP53 (82%), APC (18%), and CDK4 (15%) were the top3 co-mutant genes. What\'s more, most patients with ERBB2 fusion also had ERBB2 amplification (75.28%; 67/89), which was similar to the data in the TCGA database (88.00%; 44/50). Furthermore, TCGA database shows that patients with ERBB2 fusions in pan-cancer had a worse prognosis than those without ERBB2 fusions, as well as in breast cancer. Besides, ERBB2 amplification combined with ERBB2 fusion had worse prognosis than those with only ERBB2 amplification. ERBB2 fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with ERBB2 amplification. Prospective clinical trials are warranted to confirm the results in the future.
摘要：
ERBB2扩增是HER2靶向药物治疗的最重要和最成熟的靶标之一。酪氨酸激酶结构域中ERBB2的体细胞突变已被广泛研究,并在不同癌症类型的抗HER2治疗中发挥作用。然而,ERBB2融合尚未受到关注，其与HER2靶向治疗的相关性尚不清楚。我们从2018年5月至2021年10月的32,131种实体瘤中的下一代测序（NGS）数据全面表征了ERBB2融合。在肿瘤中，0.28%有ERBB2融合，更常见于胃食管连接部癌(3.12%;3/96)，乳腺癌（1.89%；8/422），尿路上皮癌（1.72%；1/58），和胃癌（1.60％；23/1,437）。我们的人口年龄中位数为65岁（范围为28至88岁），男性比例很高（55名男性对34名女性；61.80％）。在ERBB2融合的患者中，TP53（82%），APC（18%），和CDK4(15%)是top3共突变基因。更重要的是，大多数ERBB2融合患者也有ERBB2扩增(75.28%;67/89),这与TCGA数据库中的数据相似(88.00%;44/50)。此外，TCGA数据库显示，泛癌中ERBB2融合的患者预后比没有ERBB2融合的患者差，以及乳腺癌。此外,ERBB2扩增联合ERBB2融合的预后比仅ERBB2扩增的预后差。ERBB2融合可能干扰抗HER2靶向抗体药物的作用，影响ERBB2扩增患者的预后。未来有必要进行前瞻性临床试验以确认结果。
